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Electron crystallography of the scrapie prion protein complexed with heavy metals |
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| Authors: | Wille Holger Govaerts Cédric Borovinskiy Alexander Latawiec Diane Downing Kenneth H Cohen Fred E Prusiner Stanley B |
| Affiliation: | a Institute for Neurodegenerative Diseases, University of California, San Francisco, CA 94143, USA b Department of Neurology, University of California, San Francisco, CA 94143, USA c Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143, USA d Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143, USA e Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA |
| Abstract: | The insolubility of the disease-causing isoform of the prion protein (PrPSc) has prevented studies of its three-dimensional structure at atomic resolution. Electron crystallography of two-dimensional crystals of N-terminally truncated PrPSc (PrP 27-30) and a miniprion (PrPSc106) provided the first insights at intermediate resolution on the molecular architecture of the prion. Here, we report on the structure of PrP 27-30 and PrPSc106 negatively stained with heavy metals. The interactions of the heavy metals with the crystal lattice were governed by tertiary and quaternary structural elements of the protein as well as the charge and size of the heavy metal salts. Staining with molybdate anions revealed three prominent densities near the center of the trimer that forms the unit cell, coinciding with the location of the β-helix that was proposed for the structure of PrPSc. Differential staining also confirmed the location of the internal deletion of PrPSc106 at or near these densities. |
| Keywords: | Electron microscopy Immunolabeling Two-dimensional crystals Miniprion Uranyl binding Ammonium molybdate |
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